The overall objective of the proposed research is to study the central and periperal neural controls (both autonomic and somatic) of colonic motility and defecation and to determine how the central neural outflow is integrated with the peripheral neural plexus and colonic smooth muscle. I propose to: 1) evaluate the mechanisms under-lying the integration of autonomic and somatic inputs to the colon, sphincters, and striated muscle of the pelvic floor during defecation; 2) study the central controls of the lumbar sympathetic pathway to the large intestine (with regard to the sympathetic pathway, I plan to evaluate the cellular mechanisms for the generation of the tonic sympathetic input to the colon and determine the role of neuropeptides in central autonomic pathways); and 3) study the peripheral integrations of the central parasympathetic autonomic outflow with the intrinsic activity of colonic smooth muscle and the extramural nerve plexus. I will utilize both electrophysiological and neuro-anatomical techniques in the proposed project to study these systems. The organization of autonomic pathways within the central nervous system is a subject relatively unexplored with the recently developed electrophysiological techniques. The apparent lack of interest in these systems is most reasonable explained by the technical difficulties encountered in studying at the unit level, the small central autonomic neurons. It must be remembered, however, that a large number of human diseases arising from disorders of the nervous system involve autonomic mechanisms in one form or another; and it is therefore very important for the future rational treatment of many human illnesses the more detailed information be obtained about the neurophysiology and neuropharmacology of the central autonomic systems. It seems likely that many of the neural mechanisms which underlie the control of the large intestine may apply to other autonomic control systems as well. Therefore, the data from these experiments may provide valuable direction for future studies of other central visceral pathways.